This research project is concerned with identifying the synaptic relationships of specific fiber pathways in the spinal cord and thalamus, and determining the synaptic inputs upon certain classes of thalamic neurons. Light and electron microscopic examination of labelled axonal pathways will be used in combination with degeneration, autoradiographic, or intracellular labelling with horseradish peroxidase (HRP). In the spinal cord, the synaptic relationships formed by intracellularly labelled, physiologically characterized dorsal root axons will be carried out using electron microscopic methods. We have already labelled more than a dozen such axons in the cat and monkey and have characterized their arborizations by light microscopy. Quantitative electron microscopy will permit us to determine whether axons with unique physiological properties have unique synaptic interrelationships with spinal cord neurons. Pyramidal tract neurons will be labelled by iontophoretic techniques within the spinal white matter and the axons subsequently studied by light and electron microscopy in the cat, and subsequently in the monkey. We plan to identify the axons in the pyramidal tract which arise from either the sensory or the motor cortex and determine their projection patterns and synaptic relationships and the dorsal or ventral horns, respectively. Descending projections from the brainstem, labelled by autoradiographic methods, will be studied and their synaptic relationships with immunocytochemically characterized neurons determined. In the somatosensory thalamus (VB) we will intracellularly stain neurons which have been physiologically characterized and determine whether neurons with different physiological properties have different light microscopic morphologies. We will then examine the distribution of synapses upon the dendritic trees of these labelled neurons by electron microscopy. This work will be initially carried out in the rat and subsequently in the cat and monkey. Finally, a study of the ascending projections to monkey thalamus will be carried out autoradiographic methods.